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Cryptococcosis is a major worldwide disseminated invasive fungal infection. Cryptococcosis, particularly in its most lethal manifestation of cryptococcal meningitis, accounts for substantial mortality and morbidity. The breadth of the clinical cryptococcosis syndromes, the different patient types at-risk and affected, and the vastly disparate resource settings where clinicians practice pose a complex array of challenges. Expert contributors from diverse regions of the world have collated data, reviewed the evidence, and provided insightful guideline recommendations for health practitioners across the globe. This guideline offers updated practical guidance and implementable recommendations on the clinical approaches, screening, diagnosis, management, and follow-up care of a patient with cryptococcosis and serves as a comprehensive synthesis of current evidence on cryptococcosis. This Review seeks to facilitate optimal clinical decision making on cryptococcosis and addresses the myriad of clinical complications by incorporating data from historical and contemporary clinical trials. This guideline is grounded on a set of core management principles, while acknowledging the practical challenges of antifungal access and resource limitations faced by many clinicians and patients. More than 70 societies internationally have endorsed the content, structure, evidence, recommendation, and pragmatic wisdom of this global cryptococcosis guideline to inform clinicians about the past, present, and future of care for a patient with cryptococcosis., Competing Interests: Declaration of interests AA reports grants from the Agence Nationale de la Recherche; serving as a consultant to Gilead Sciences; receiving speaking honoraria from Gilead Sciences and PR Edition; travel support from Gilead sciences and Pfizer; and patents with the Institut Pasteur. J-WA reports grants or contracts from WHO (fungal priority pathogens list) and receipt of equipment and materials from the Westmead Hospital Foundation. JB reports support from the Australian National Health and Medical Research Council and receipt of honoraria from Gilead. TAB reports a personal research fellowship from Gilead Sciences; investigator-led research grant from Pfizer; lecture honoraria and participation in advisory boards for Gilead Sciences, Mundipharma, and Pfizer; and participation in the Trial Steering Committee for a phase 2 trial of inhaled opelconazole (Pulmocide). FC reports speaker honoraria from, and being part of, an advisory board for Pfizer and United Medical. CCC reports receipt of an Early Career Fellowship from the Australian National Health and Medical Research Foundation, receipt of a speaker travel support for IDweek 2024, being a principal investigator in an early phase clinical trial unit, and was a recipient of the Australian National Health and Medical Research Council Early Career Fellowship (APP 1092160). MC reports grants from Cidara, F2G, Pfizer, and Janssen; receipt of honoraria from Pfizerm MSD and Gilead; and travel support from Pfizer. SCC reports untied educational grants from MSD Australia and F2G and is on the antifungal advisory boards of MSD Australia, Gilead Sciences, and F2G. OAC reports grants or contracts from BMBF, Cidara, EU-DG RTD (101037867), F2G, Gilead, MedPace, MSD, Mundipharma, Octapharma, Pfizer, and Scynexis; consulting fees from AbbVie, AiCuris, Biocon, Cidara, Gilead, IQVIA, Janssen, Matinas, MedPace, Menarini, Moderna, Molecular Partners, MSG-ERC, Noxxon, Octapharma, Pfizer, PSI, Scynexis, and Seres; honoraria for lectures from Abbott, AbbVie, Al-Jazeera Pharmaceuticals, Hikma, Gilead, Grupo Biotoscana/United Medical/Knight, MedScape, MedUpdate, Merck/MSD, Noscendo, Pfizer, Shionogi, and streamedup!; payment for expert testimony from Cidara; participation on a data safety monitoring board or advisory board from Boston Strategic Partners, Cidara, IQVIA, Janssen, MedPace, PSI, Pulmocide, Shionogi, and The Prime Meridian Group; a patent at the German Patent and Trade Mark Office (DE 10 2021 113 007·7); stocks from CoRe Consulting and EasyRadiology; other interests from Wiley; support from the German Federal Ministry of Research and Education; and funding by the Deutsche Forschungsgemeinschaft under Germany's Excellence Strategy (Cologne Cluster of Excellence on Cellular Stress Responses in Aging-associated Diseases, EXC 2030—390661388). J-PG reports speaker honoraria from Gilead, MundiPharma, and Pfizer. NPG reports grants from National Institutes of Health (USA), National Institute of Health and Care Research (UK), Medical Research Council (MRC; UK), Centers for Disease Control and Prevention (CDC; USA), and National Health Laboratory Service Research Trust (South Africa); participation in the ACACIA trial as part of the data safety monitoring board, project committee of DREAMM, project advisory committee for 5FC Crypto, and leadership roles in the Federation of Infectious Diseases Societies of Southern Africa. AHG reports grants from Gilead Sciences; personal fees from Amplyx, Astellas, Basilea, F2G, Gilead Sciences, Merck Sharp & Dohme, Mundipharma, Pfizer, and Scynexis; speaker honoraria from Gilead Sciences and MSD; and participation in an advisory board for Astellas, Mundipharma, Partner Therapeutics, and Pfizer. FH reports grants from Health Holland and European Society for Clinical Microbiology and Infectious Diseases; leadership roles as treasurer of the Netherlands Society for Medical Mycology, Chair of the Division Microbial Genomics of the Royal Netherlands Society for Microbiology, Vice-President International Society for Human and Animal Mycology (ISHAM); and receipt of evaluation kits from Bruker and Pathonostics. TSH reports receipt of an investigator award from Gilead Sciences, honoraria from Pfizer and Gilead Sciences, and participation in a data safety monitoring board or advisory board for Viamet and F2G. MH reports receipt of an European and Developing Countries Clinical Trials Partnership. JNJ reports support from the National Institute for Health Research; grants from European and Developing Countries Clinical Trials Partnership, joint global health trials (Wellcome Trust, MRC, and UK aid) and CDC; speaker fees from Gilead Sciences; participation on a data safety and monitoring board for the HARVEST, ARTIST, CASTLE, and ACACIA trials. GJ reports travel support to attend a meeting at ISHAM. NK was a speaker and advisor for Gilead Sciences, Merck/MSD, and Pfizer and a speaker for Astellas. MSL reports support from the Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), and National Institutes of Health (NIH). OL reports receipt of consulting fees and honoraria from Gilead Science and patents with INSERM APHP. OMM reports travel support for ISHAM meeting in India and being the country ambassador for Kenya for ISHAM. BJM reports being chair of the Australia and New Zealand Paediatric Infectious Diseases Group. DBM reports leadership role in the Crypto Meningitis advocacy group. RO reports receiving research and educational grant funding from Gilead Sciences, CDC Atlanta, and Pfizer Specialties and travel support from the CDC foundation. PGP reports grants from Mayne, Astellas, Scynexis, and Cidara and receipt of consulting fees from F2G and Cidara. AKP reports speaker honoraria for Gilead Science, Pfizer India, and Intas pharmaceutical. JRP reports grants from NIH, Appili, and Sfunga; royalties from Up-To-Date; and participation on a data safety monitoring board or advisory board from Pulmocide, EFFECT trial, and IMPRINT trial. FQ-TF reports receipt of speaker honoraria from Pfizer and United Medical, travel support and laboratory diagnostic kits from IMMY, and leadership roles in Infocus Latin America. JS-G reports speaker honoraria from Gilead and Pfizer and is on an advisory committee for Pfizer. AS reports grants from Astellas and receiving consulting fees from Scynexis. RSp has received speaker honoraria from Pfizer and reports being chair of Young European Confederation of Medical Mycology. TT reports receipt of honoraria from Pfizer, MSD, Asahikasei pharma, and Sumitomo pharma. AW reports a grant from UK Research and Innovation; receipt of consultant fees from Gilead and MundiPharma; speaker fees from F2G and Gilead; and participation as a data safety monitoring board member for the RECOVERY trial. All declarations are outside the submitted work. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Competing Interests: The authors declare no competing interests.

Uncommon, or rare, yeast infections are on the rise given increasing numbers of patients who are immunocompromised or seriously ill. The major pathogens include those of the genera Geotrichum, Saprochaete, Magnusiomyces, and Trichosporon (ie, basidiomycetes) and Kodamaea, Malassezia, Pseudozyma (ie, now Moesziomyces or Dirkmeia), Rhodotorula, Saccharomyces, and Sporobolomyces (ie, ascomycetes). A considered approach to the complex, multidisciplinary management of infections that are caused by these pathogens is essential to optimising patient outcomes; however, management guidelines are either region-specific or require updating. In alignment with the One World-One Guideline initiative to incorporate regional differences, experts from diverse geographical regions analysed publications describing the epidemiology and management of the previously mentioned rare yeasts. This guideline summarises the consensus recommendations with regards to the diagnostic and therapeutic options for patients with these rare yeast infections, with the intent of providing practical assistance in clinical decision making. Because there is less clinical experience of patients with rare yeast infections and studies on these patients were not randomised, nor were groups compared, most recommendations are not robust in their validation but represent insights by use of expert opinions and in-vitro susceptibility results. In this Review, we report the key features of the epidemiology, diagnosis, antifungal susceptibility, and treatment outcomes of patients with Geotrichum, Saprochaete, Magnusiomyces, and Trichosporon spp infections., Competing Interests: Declaration of interests KA, DEA, JC, LD-G, CG, P-RH, MI, SSK, OL, LP, TP, RR-R, MR, JS-G, ES, DS, AS, IS, RS, JS, ET, LT, AMT, MH, and FFT declare no competing interests. SA-A reports speaker honoraria from Gilead Sciences and travel grants from Astellas and Pfizer, outside the submitted work. TB reports grants from Gilead Sciences and personal fees from Gilead Sciences and Pfizer, outside the submitted work. SC-AC reports untied educational grants from Merck Sharp and Dohme Australia and F2G and is on the antifungal advisory boards of Merck Sharp and Dohme Australia, Gilead Sciences, and F2G, outside the submitted work. ALC reports grants from Astellas and Pfizer; personal fees from Astellas, Pfizer, Eurofarma, Merck Sharp and Dohme, Gilead Sciences, and Biotoscana-United Medical; and non-financial support from Eurofarma, Gilead Sciences, and Biotoscana-United Medical, outside the submitted work. OAC is supported by the German Federal Ministry of Research and Education; is funded by the Deutsche Forschungsgemeinschaft under Germany's Excellence Strategy (Cologne Cluster of Excellence on Cellular Stress Responses in Aging-associated Diseases, EXC 2030—390661388); has received research grants from Actelion, Amplyx, Astellas, Basilea, Cidara, Da Volterra, F2G, Gilead Sciences, Janssen, Medicines Company, Melinta, Merck/Merck Sharp and Dohme, Octapharma, Pfizer, and Scynexis; is a consultant to Actelion, Allecra, Amplyx, Astellas, Basilea, Biosys, Cidara, Da Volterra, Entasis, F2G, Gilead Sciences, Matinas, MedPace, Menarini, Merck/Merck Sharp and Dohme, Mylan, Nabriva, Noxxon, Octapharma, Paratek, Pfizer, PSI, Roche Diagnostics, Scynexis, and Shionogi; and has received lecture honoraria from Al-Jazeera Pharmaceuticals, Astellas, Basilea, Gilead Sciences, Grupo Biotoscana, Merck/Merck Sharp and Dohme, and Pfizer, outside the submitted work. JNdAJ reports grants from Fundação de Amparo à Pesquisa do Estado de São Paulo, outside the submitted work. TF reports grants from Ministry of Health, Czech Republic, outside the submitted work. GG-E reports grants from Gador SA Laboratory (Argentina) and travel grants from Pfizer and Grupo Biotoscana, outside the submitted work. NG reports honoraria from Merck Sharp and Dohme, Australia, in 2019 and has participated in educational activities under the auspices of the Australia–New Zealand Mycology Interest Group. The Australia–New Zealand Mycology Interest Group workshops and meetings receive pharmaceutical sponsorship (from Pfizer, Gilead Sciences, Merck Sharp and Dohme, and Mayne Pharma), outside the submitted work. NPG reports grants from the National Institutes of Health, US Center for Disease Control and Prevention, Bill & Melinda Gates Foundation, UK Medical Research Council, and National Health Laboratory Service Research Trust and non-financial support from Gilead Sciences, outside the submitted work. AHG reports grants from Gilead Sciences, Merck Sharp and Dohme, and Pfizer and personal fees from Amplyx, Astellas, Basilea, Gilead Sciences, Merck Sharp and Dohme, Pfizer, F2G, and Synexis, outside the submitted work. CL-F reports grants from Gilead Sciences and Astellas and personal fees from Gilead Sciences, Astellas, Merck Sharp and Dohme, Basilea, and Angelini, outside the submitted work. JM reports grants from Astellas, Gilead Sciences, Merck Sharp and Dohme, and Pfizer, outside the submitted work. PM reports personal fees from Angelini, Basilea, Gilead Sciences, Merck Sharp and Dohme, Nabriva, Pfizer, and Fundación Ciencias de la Salud, outside the submitted work. LO-Z reports grants from Cidara, Scynexis, Amplyx, Pfizer, and Astellas and personal fees from Cidara, Scynexis, F2G, Pfizer, Astellas, Merck, and Gilead Sciences, outside the submitted work. JP reports grants from Merck, Astellas, Pfizer, Amplyx, and Minnetronix and personal fees from Merck, F2G, Scynexis, Amplyx, and Ampili, outside the submitted work. AV reports research grants from Procter and Gamble, L'Oréal Paris, Pfizer, and Astellas and honorarium from Merck Sharp and Dohme, outside the submitted work. NW reports grants from Astellas, bioMerieux, Cepheid, Cidara, Covance, F2G, and Viamet and personal fees from Gilead Sciences and Mayne Pharma, outside the submitted work. Y-CC reports personal fees for lectures from Pfizer, Merck Sharp and Dohme, and Gilead Sciences, outside the submitted work., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

In 2018, WHO issued guidelines for the diagnosis, prevention, and management of HIV-related cryptococcal disease. Two strategies are recommended to reduce the high mortality associated with HIV-related cryptococcal meningitis in low-income and middle-income countries (LMICs): optimised combination therapies for confirmed meningitis cases and cryptococcal antigen screening programmes for ambulatory people living with HIV who access care. WHO's preferred therapy for the treatment of HIV-related cryptococcal meningitis in LMICs is 1 week of amphotericin B plus flucytosine, and the alternative therapy is 2 weeks of fluconazole plus flucytosine. In the ACTA trial, 1-week (short course) amphotericin B plus flucytosine resulted in a 10-week mortality of 24% (95% CI -16 to 32) and 2 weeks of fluconazole and flucytosine resulted in a 10-week mortality of 35% (95% CI -29 to 41). However, with widely used fluconazole monotherapy, mortality because of HIV-related cryptococcal meningitis is approximately 70% in many African LMIC settings. Therefore, the potential to transform the management of HIV-related cryptococcal meningitis in resource-limited settings is substantial. Sustainable access to essential medicines, including flucytosine and amphotericin B, in LMICs is paramount and the focus of this Personal View., (Copyright © 2019 Elsevier Ltd. All rights reserved.)